Regulation of skeletal muscle regeneration by chemoreceptors and odorant receptors 公开
Griffin, Christine Annette (2010)
Abstract
Skeletal muscle is a complex and highly organized tissue that is necessary for locomotion, metabolism and breathing. Myogenesis, the formation of skeletal muscle, occurs during muscle development, remodeling and regeneration in the adult. Many processes are required for proper myofiber formation, including migration and adhesion. In this dissertation, we demonstrated that many chemokines and chemokine receptors are expressed by muscle cells in vitro. The large number of migratory factors expressed by muscle cells suggests a complex temporal and spatial control of muscle cell migration during myogenesis. These data also determine a specific role for CXCR4 and SDF1α during myogenesis. The migration of both proliferating and terminally differentiated muscle cells is regulated by CXCR4 and SDF1α. Also, in this dissertation, we determined that at least 13 olfactory receptors (ORs) are expressed during myogenesis. Furthermore, one specific OR, MOR23 regulates both migration and adhesion, affecting proper myogenesis. MOR23 also affects a phenomenon known as myofiber branching, where a myofiber is contiguous with several smaller myofibers. Myofiber branching is increased with multiple injuries, aging and muscular dystrophies and decreases the contractile force of the myofiber. Over-expression of MOR23 decreases the incidence of myofiber branching in regenerating muscle, suggesting potential options for treating various muscle diseases. Therefore, manipulation of either chemokines or ORs may allow for an increased efficiency of cell transplantation therapies for various muscle disorders.
Table of Contents
Table of Contents
Chapter 1: Introduction...1
Chapter 2: Background and Significance...5
Skeletal muscle structure and function...6
Myogenesis in the embryo and adult...7
Branched myofibers during myogenesis...13
Migration and adhesion during myogenesis...15
Migration during embryogenesis...15
Migration during adult regenerative myogenesis...17
Migration of transplanted muscle cells...19
Migratory factors for muscle cells...23
Migration signaling during myogenesis...32
Regulation of migration by the extracellular matrix...36
Role of chemokine ligands and receptors during myogenesis...39
Chemokines and migration...40
Chemokines and muscle...41
CXCR4/SDF1α axis in muscle...44
Cell-cell adhesion during myogenesis...46
Characteristics and functions of olfactory receptors...48
Types of ligands for ORs...49
ORs and axon guidance...50
Ectopic expression of ORs...53
ORs and sperm...54
Chapter 3: Materials and Methods...56
Chapter 4: Myoblasts versus myocytes paper...74
Introduction...75
Results...78
Discussion...86
Chapter 5: MOR23 promotes muscle regeneration and regulates cell adhesion and migration...107
Introduction...108
Results...109
Discussion...123
Chapter 6: Discussion...165
References...184
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